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Lippincott Illustrated Reviews: Pharmacology 6th Edition



Lippincott Illustrated Reviews: Pharmacology 6th Edition

Author: Karen Whalen

Publisher: LWW

Genres:

Publish Date: October 10, 2018

ISBN-10: 149638413X

Pages: 576

File Type: PDF

Language: English

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Book Preface

Pharmacokinetics refers to what the body does to a drug, whereas pharmacodynamics (see Chapter 2) describes what the drug does to the body. Four pharmacokinetic properties determine the onset, intensity, and the duration of drug action (Figure 1.1):
• Absorption: First, absorption from the site of administration permits entry of the drug (either directly or indirectly) into plasma.
• Distribution: Second, the drug may then reversibly leave the bloodstream and distribute into the interstitial and intracellular fluids.
• Metabolism: Third, the drug may be biotransformed by metabolism by the liver or other tissues.
• Elimination: Finally, the drug and its metabolites are eliminated from the body in urine, bile, or feces. Using knowledge of pharmacokinetic parameters, clinicians can design optimal drug regimens, including the route of administration, the dose, the frequency, and the duration of treatment.

The route of administration is determined by the properties of the drug (for example, water or lipid solubility, ionization) and by the therapeutic objectives (for example, the desirability of a rapid onset, the need for long-term treatment, or restriction of delivery to a local site). Major routes of drug administration include enteral, parenteral, and topical, among others (Figure 1.2).

Enteral
Enteral administration (administering a drug by mouth) is the safest and most common, convenient, and economical method of drug administration. The drug may be swallowed, allowing oral delivery, or it may be placed under the tongue (sublingual), or between the gums and cheek (buccal), facilitating direct absorption into the bloodstream.
1. Oral: Oral administration provides many advantages. Oral drugs are easily self-administered, and toxicities and/or overdose of oral drugs may be overcome with antidotes, such as activated charcoal. However, the pathways involved in oral drug absorption are the most complicated, and the low gastric pH inactivates some drugs. A wide range of oral preparations is available including enteric-coated and extended-release preparations.
a. Enteric-coated preparations: An enteric coating is a chemical envelope that protects the drug from stomach acid, delivering it instead to the less acidic intestine, where the coating dissolves and releases the drug. Enteric coating is useful for certain drugs (for example, omeprazole) that are acid unstable. Drugs that are irritating to the stomach, such as aspirin, can be formulated with an enteric coating that only dissolves in the small intestine, thereby protecting the stomach.
b. Extended-release preparations: Extended-release (abbreviated ER or XR) medications have special coatings or ingredients that control the drug release, thereby allowing for slower absorption and a prolonged duration of action. ER formulations can be dosed less frequently and may improve patient compliance.

Additionally, ER formulations may maintain concentrations within the therapeutic range over a longer period of time, as opposed to immediate-release dosage forms, which may result in larger peaks and troughs in plasma concentration. ERformulations are advantageous for drugs with short half-lives. For example, the half-life of oral morphine is 2 to 4 hours, and it
relief. However, only two doses are needed when extendedrelease tablets are used. Unfortunately, many ER formulations have been developed solely for a marketing advantage over immediate-release products, rather than a documented clinical advantage.
2. Sublingual/buccal: Placement under the tongue allows a drug to diffuse into the capillary network and enter the systemic circulation directly. Sublingual administration has several advantages, including ease of administration, rapid absorption, bypass of the harsh gastrointestinal (GI) environment, and avoidance of firstpass metabolism (see discussion of first-pass metabolism below). The buccal route (between the cheek and gum) is similar to the sublingual route.


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